Until recently the manifestations of cerebral senility have been thought to result from arteriosclerosis with a subsequent diminution of adequate oxygen delivery to the nervous tissue, Terry (1980). However, it is now apparent that (in at least some individuals' central nervous systems) cerebral "aging" (loss of cognitive function) is due to primary degenerative functional deficiencies in the neural cells (neurons) themselves, Whitehouse (1982). These deficiencies, when so severe as to merit being categorized separately due to the severe defect in recent memory recall and cognitive function, are termed Alzheimer's syndrome, Kateman (1976). In dementia of the Alzheimer's type, also referred to as Alzheimer's disease (AD), neuropathological brain examinations in most but not all patients have revealed some characteristic abnormalities, e.g., neuritic plaques, abnormal neurites, neurofibrillary tangles containing paired helical filaments composed of cross-linked polypeptides, that are especially prominent in the cerebral cortex and hippocampal formation, Perry (1977). In the last decade, it has been found that excessive nerve cell loss occurs in the frontal and temporal cortices of the cerebral cortex. Recently, it has been demonstrated that there seems to be a relatively specific loss (75 percent) of the neurons in the basal nucleus of Meynert, Coyle (1983). The cells affected are the major source of extrinsic cholinergic input into the cortex.
A recent article by Goldsmith, "Attempts to Vanquish Alzheimer's Disease Intensify, Take New Paths," refers to AD as a "dementing disorder for which the diagnosis is unequivocal only post-mortem, the therapy almost non-existent, and prognosis grim." JAMA 251: 1805 (Apr. 13, 1984).
Presently, AD is generally diagnosed on the basis of behavioral symptoms and psychological scoring. The diagnosis may be reinforced by morphological examination of the brain (by noninvasive methods like CAT scan) for structural abnormalities (frontal lobe cortical atrophy). In addition, biochemical examination of cerebrospinal fluid may reveal depressed levels of the enzymes choline acetyltransferase and/or acetylcholine esterase. After death, the presence of AD may be established unequivocally by the detection of atrophy of the basal nucleus of Meynert.
Research, and therapeutic efforts as well, are currently focused on efforts to facilitate the release of acetylcholine from the undegenerated neurons as well as ultimately preventing the progressive deterioration of these neurons. However, studies of more fundamental immunobiology may be more rewarding. For example, each of the major class of "immunocytes", i.e., monocytes, natural killer cells, B lymphocytes, suppressor T-cells and helper T-cells appear to have an antigenic counterpart in CNS cells, but in cells of no other organ.